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3.
J Breath Res ; 10(2): 026007, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27082636

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive deterioration of the alveolar integrity. Among IPF identified phenotypes, that of familial (f-)IPF is usually associated with several gene mutations which are seldom observed in sporadic (s-)IPF. This study aimed at investigating the molecular patterns and variability in f-IPF and s-IPF patients through a differential proteomic analysis. Protein patterns of bronchoalveolar lavage fluid (BALF) samples from 10 familial and 17 sporadic IPF patients were compared using 2D electrophoresis and mass spectrometry. Principal component analysis (PCA) was applied to proteomic data and an enrichment analysis was also performed to characterize specific pathogenic mechanisms and to identify potential biomarkers. BALF samples from f-IPF showed 87 protein spots differentially expressed than those from s-IPF samples; once identified, these spots revealed 22 unique proteins. The functional analysis showed that the endothelial reticulum stress probably plays a central pathogenetic role in f-IPF with an up-regulation of proteins involved in wounding and immune responses, coagulation system, and ion homeostasis. Up-regulated proteins in the s-IPF group were those involved in the oxidative stress response. PCA analysis of differentially expressed proteins clearly distinguished f-IPF from s-IPF patients, and in agreement with radiological and histological patterns, pointed out a higher heterogeneity in f-IPF than s-IPF samples. The 'Slit/Robo signaling', 'clathrin-coated vesicle' and 'cytoskeleton remodelling', were extrapolated by 'pathways analysis' and the results of 'diseases (by biomarkers)' highlighted a 'connective tissue and autoimmune disease', two aspects of increasing interest in IPF.


Assuntos
Líquido da Lavagem Broncoalveolar , Fibrose Pulmonar Idiopática/metabolismo , Estresse Oxidativo/fisiologia , Proteômica , Biomarcadores/análise , Lavagem Broncoalveolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxirredução
4.
J Proteomics ; 128: 375-87, 2015 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-26342673

RESUMO

Pulmonary sarcoidosis (Sar) is an idiopathic disease histologically typified by non-caseating epitheliod cell sarcoid granulomas. A cohort of 37 Sar patients with chronic persistent pulmonary disease was described in this study. BAL protein profiles from 9 of these Sar patients were compared with those from 8 smoker (SC) and 10 no-smoker controls (NSC) by proteomic approach. Principal Component Analysis was performed to clusterize the samples in the corresponding conditions highlighting a differential pattern profiles primarily in Sar than SC. Spot identification reveals thirty-four unique proteins involved in lipid, mineral, and vitamin Dmetabolism, and immuneregulation of macrophage function. Enrichment analysis has been elaborated by MetaCore, revealing 14-3-3ε, α1-antitrypsin, GSTP1, and ApoA1 as "central hubs". Process Network as well as Pathway Maps underline proteins involved in immune response and inflammation induced by complement system, innate inflammatory response and IL-6signalling. Disease Biomarker Network highlights Tuberculosis and COPD as pathologies that share biomarkers with sarcoidosis. In conclusion, Sar protein expression profile seems more similar to that of NSC than SC, conversely to other ILDs. Moreover, Disease Biomarker Network revealed several common features between Sar and TB, exhorting to orientate the future proteomics investigations also in comparative BALF analysis of Sar and TB.


Assuntos
Proteoma/metabolismo , Proteômica/métodos , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/metabolismo , Fumar/metabolismo , Tuberculose/metabolismo , Líquido da Lavagem Broncoalveolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sarcoidose Pulmonar/complicações , Sensibilidade e Especificidade , Transdução de Sinais
5.
Respir Med ; 109(9): 1224-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26224473

RESUMO

BACKGROUND: Exhaled nitric oxide (eNO) and carbon monoxide (eCO) are markers of pulmonary inflammation associated with acute graft rejection and lung infections in lung transplant (LTX) recipients. Regarding eNO and eCO levels in LTX patients affected by bronchiolitis obliterans syndrome (BOS), published data are discordant. OBJECTIVES: We aim to evaluate eNO at multiple flows, alveolar concentration of nitric oxide (CalvNO), maximum conducting airway wall flux (J'awNO) and eCO levels in LTX patients to assess the potential role of these parameters in BOS evaluation. METHODS: Fractional exhaled nitric oxide (FeNO), CalvNO and J'awNO were analysed in 30 healthy subjects and 27 stable LTX patients (12 BOS patients). Pulmonary function tests were performed after eNO and eCO assessment. Receiver operating characteristic (ROC) curves were conducted to evaluate diagnostic accuracy for BOS of eNO parameters. RESULTS: LTX patients reported higher values of FeNO at flow rates of 50 (p < 0.01), 150 (p < 0.05), 350 ml/s (p < 0.001), and CalvNO (p < 0.0001) than healthy controls. BOS patients showed higher FeNO at flow rates of 150 (p < 0.05) and 350 ml/s (p < 0.01) and CalvNO (p < 0.001) than non-BOS patients. CalvNO reported a remarkable diagnostic accuracy for BOS (AUC: 0.82). There were no significant differences of eCO levels between LTX patients and healthy controls. CONCLUSION: LTX patients affected by BOS showed higher levels of FeNO 150 and 350, and CalvNO than non-BOS LTX patients, probably due to chronic airway inflammation and fibrotic remodelling. CalvNO may be a potential biomarker of BOS in LTX patients.


Assuntos
Bronquiolite Obliterante/diagnóstico , Monóxido de Carbono/metabolismo , Transplante de Pulmão/efeitos adversos , Óxido Nítrico/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Testes Respiratórios/métodos , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/fisiopatologia , Estudos de Casos e Controles , Expiração/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória
6.
Respir Physiol Neurobiol ; 197: 46-52, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24703971

RESUMO

Nitric oxide (NO) is a biomarker of nitrosative stress, which is involved in the pathogenesis of idiopathic interstitial pneumonias (IIP). This study evaluates exhaled NO levels in IIP patients and relates alveolar concentrations of NO (CalvNO) to pulmonary function test (PFT) and 6-minute walking test (6MWT) parameters. We measured fractional exhaled nitric oxide (FeNO), CalvNO and maximum conducting airway wall flux (J'awNO) in 30 healthy subjects and 30 patients with IIP (22 idiopathic pulmonary fibrosis and 8 idiopathic non-specific interstitial pneumonias). IIP patients had higher FeNO at flow rates of 50-100-150 ml/s and higher CalvNO levels than healthy controls (p<0.0001). CalvNO was significantly correlated with 6-minute walking distance (p<0.0001), recovery time (p<0.0005), TLC (p<0.001), FVC (p=0.01) and TLCO (p<0.01). IIP patients showed abnormal nitric oxide production, probably due to lung fibrosis and oxidative-mediated lung injury. CalvNO was correlated with PFT and 6MWT parameters and is proposed as a potential biomarker of lung fibrosis and exercise tolerance.


Assuntos
Fibrose Pulmonar Idiopática/metabolismo , Doenças Pulmonares Intersticiais/metabolismo , Óxido Nítrico/análise , Biomarcadores/metabolismo , Testes Respiratórios , Teste de Esforço , Expiração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fatores de Tempo , Caminhada
7.
Inflammation ; 37(1): 10-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23912648

RESUMO

Recent literature and our previous proteomic findings prompted us to study the coagulation system in idiopathic pulmonary fibrosis (IPF), the pathogenesis of which remains unclear. The aim of this study was to compare coagulation factors in idiopathic pulmonary fibrosis and idiopathic nonspecific interstitial pneumonia (NSIP) patients and healthy controls. Thirty-three IPF patients (23 acute exacerbation and 10 stable IPF patients), 7 NSIP patients, and 44 controls were enrolled. Concentrations of D-dimer, homocysteine, functional protein C, protein C antigen, free and total protein S antigen and activity, fibrinogen and factor VIIIc were analyzed in serum of patients and controls. The lupus anticoagulant (LAC) test was also performed. Factor VIIIc levels were significantly higher in acute exacerbation IPF patients than controls (p = 0.0001) and in stable IPF patients than controls (p = 0.002). Factor VIIIc levels were higher and PT levels were lower in acute exacerbation IPF patients who died after exacerbation than in patients who survived (p = 0.04 and p = 0.003, respectively). D-dimer, fibrinogen, and homocysteine levels were also significantly higher in IPF patients than controls (p < 0.01). Protein C activity was increased in acute exacerbation IPF patients than controls (p = 0.005). The LAC test was positive in seven IPF patients and negative in controls. Procoagulant status was demonstrated in IPF patients (mainly in acute exacerbation/IPF) than controls and NSIP patients, probably due to endothelial activation and microvascular injury. These preliminary results are of interest because of their potential implications in the pathogenesis and treatment of this disease.


Assuntos
Fatores de Coagulação Sanguínea/análise , Coagulação Sanguínea/fisiologia , Pneumonias Intersticiais Idiopáticas/sangue , Fibrose Pulmonar Idiopática/sangue , Fator VIII/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Homocisteína/sangue , Humanos , Pneumonias Intersticiais Idiopáticas/mortalidade , Fibrose Pulmonar Idiopática/mortalidade , Inibidor de Coagulação do Lúpus/sangue , Masculino , Pessoa de Meia-Idade , Proteína C/análise , Proteína S/análise
8.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(2): 157-61, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24071890

RESUMO

Sarcoidosis is a multi-factorial systemic disease with increased activity of the cellular immune components which is responsible of the formation of non-caseating granulomas in involved organs. Recent views on the etiology indicate interactions between inherited susceptibility and environmental or lifestyle factors. Concerning genes that may influence susceptibility to sarcoidosis Toll-like receptors (TLRs) may represent plausible candidates. In this present study, we investigated the X-linked TLR7 rs179008/Gln11Leu polymorphism situated on exon 3. SNP genotyping of the TLR7 exon polymorphism was performed by TaqMan allelic discrimination using the StepOnePlus™ Real-Time PCR System (Applied Biosystems). In females, the incidence of the AT genotypes of the polymorphism was significantly lower in sarcoidosis patients compared to control subjects  (P=0.0001). We could observe in control subjects a significant preponderance of the T allele of the TLR7 rs179008/Gln11Leu polymorphism compared to sarcoidosis female patients (P=0.008). In males, no significant differences between patients and controls emerged in allele frequencies of the TLR7 rs179008/Gln11Leu polymorphism. The presence of the TLR7 rs179008/Gln11Leu polymorphism in sarcoidosis may determine an alteration of TLR7 function hampering the signaling pathway involved in the onset of both cellular and humoral autoimmunity. This is consistent with the view that in some circumstances genetic mutations affecting components of the immune system can prevent systemic autoimmunity.


Assuntos
Polimorfismo de Nucleotídeo Único , Sarcoidose/genética , Receptor 7 Toll-Like/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino
9.
J Proteomics ; 83: 60-75, 2013 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-23528693

RESUMO

Bronchoalveolar lavage fluid of patients with four interstitial lung diseases (sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis) and smoker and non smoker control subjects were compared in a proteomic study. Principal component analysis was used to statistically verify the association between differentially expressed proteins and the conditions analyzed. Pathway and functional analysis by MetaCore and DAVID software revealed possible regulatory factors involved in specific "process networks" like regulation of stress and inflammatory responses. Immune response by alternative complement pathways, protein folding, Slit-Robo signaling and blood coagulation were "pathway maps" possibly associated with interstitial lung diseases pathogenesis. Four interesting proteins plastin 2, annexin A3, 14-3-3ε and S10A6 (calcyclin) were validated by Western blot analysis. In conclusion, we identified proteins that could be directly or indirectly linked to the pathophysiology of the different interstitial lung diseases. Multivariate analysis allowed us to classify samples in groups corresponding to the different conditions analyzed and based on their differential protein expression profiles. Finally, functional and pathway analysis defined the potential function and relations among identified proteins, including low abundance molecules present in the MetaCore database. BIOLOGICAL SIGNIFICANCE: This is the first study where different interstitial lung diseases such as sarcoidosis, idiopathic pulmonary fibrosis, pulmonary Langerhans cell histiocytosis, fibrosis associated to systemic sclerosis and smoker and non smoker control subjects were compared in a proteomic study to highlight their common pathways. We decided to report not only principal component analysis, used to statistically verify the association between differentially expressed proteins and the conditions analyzed, but also functional analysis general results, considering all differential proteins potentially involved in these conditions, to speculate about possible common pathogenetic pathways involved in fibrotic lung damage.


Assuntos
Regulação da Expressão Gênica , Histiocitose de Células de Langerhans/metabolismo , Pulmão/metabolismo , Proteoma/biossíntese , Proteômica/métodos , Fibrose Pulmonar/metabolismo , Sarcoidose/metabolismo , Idoso , Bases de Dados de Proteínas , Feminino , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/fisiopatologia , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fibrose Pulmonar/patologia , Fibrose Pulmonar/fisiopatologia , Sarcoidose/patologia , Sarcoidose/fisiopatologia , Fumar/metabolismo , Fumar/patologia , Fumar/fisiopatologia , Software
10.
Int J Immunopathol Pharmacol ; 25(3): 681-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23058018

RESUMO

The aims of the present study are to define the prevalence of pulmonary hypertension (PH) in a cohort of idiopathic pulmonary fibrosis (IPF) patients, to investigate any correlations between systolic pulmonary artery pressure (PAPs) and functional data, to evaluate clinical progress and to compare long-term survival in IPF patients with and without PH. A population of 126 IPF patients was recruited. A high prevalence of PH (39.7%, 50/126), evaluated by echocardiography on the basis of PAPs greater than 36 mmHg, was mainly observed in smokers and female patients. Regression analysis revealed a significant correlation between PAPs greater than 50 mmHg and DLCO/VA (p = 0.0294). Mean PAPs was significantly greater one year after onset of PH (p = 0.01). 11/21 patients with FVC less than 50% had a significant increase in PAPs one year after onset of PH (p = 0.02). There was a highly significant difference between survival of IPF patients with and without PH (p = 0.0001; hazard ratio = 3.56). This study revealed that PH has a high prevalence in patients with IPF and is associated with increased risk of mortality. Early diagnosis of IPF patients with pulmonary hypertension is important, so that they can be enrolled in waiting lists for lung transplant as soon as possible.


Assuntos
Hipertensão Pulmonar/epidemiologia , Fibrose Pulmonar Idiopática/epidemiologia , Idoso , Pressão Arterial , Distribuição de Qui-Quadrado , Progressão da Doença , Diagnóstico Precoce , Feminino , Volume Expiratório Forçado , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/mortalidade , Fibrose Pulmonar Idiopática/fisiopatologia , Itália/epidemiologia , Estimativa de Kaplan-Meier , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Prognóstico , Artéria Pulmonar/fisiopatologia , Capacidade de Difusão Pulmonar , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Capacidade Pulmonar Total , Capacidade Vital
11.
Eur J Radiol ; 81(8): 1907-12, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21549535

RESUMO

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare disease that occurs almost exclusively in smokers, generally young adults between 20 and 40 years old. Prognostic biomarkers of the disease are lacking. This study describes the clinical-radiological features of a group of PLCH patients and applies a semi-quantitative CT score of the chest to verify the prognostic value of radiological findings in this disease. Clinical-radiological and immunological data from 12 Caucasian patients (6M, 7 smokers and 5 ex-smokers, mean age 36±8 years) were recorded at onset and after a follow-up period of 4 years. Application of the semi-quantitative CT score revealed a prevalently cystic pattern at onset and follow-up in the majority of the patients. Patients with a prevalently nodular pattern developed cystic lesions during follow-up. Interestingly, significant correlations were found between the extent of cystic lesions and DLCO values at onset (time 0: p<0.05) and at the end of follow-up (time 1, p<0.05) and with FEV1 values at time 0 (p<0.05) and time 1 (p<0.05). Patients with progressive functional decline were those with CT evidence of severe cystic alterations. The results suggest that high resolution CT scan of the chest is mandatory for characterizing PLCH patients at diagnosis and during follow-up. The proposed CT score of the chest showed potential prognostic value.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico por imagem , Tomografia Computadorizada Espiral/métodos , Adulto , Feminino , Seguimentos , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
12.
Sarcoidosis Vasc Diffuse Lung Dis ; 28(1): 56-64, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21796892

RESUMO

The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.


Assuntos
Comitês Consultivos , Predisposição Genética para Doença , Pneumologia , Sarcoidose Pulmonar , Adolescente , Adulto , Idoso , Criança , Congressos como Assunto , Diagnóstico Diferencial , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade , Fenótipo , Estudos Retrospectivos , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/epidemiologia , Sarcoidose Pulmonar/genética , Adulto Jovem
13.
Rheumatol Int ; 31(12): 1539-44, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21644041

RESUMO

Sarcoidosis is a granulomatous lung disease in which several cytokines play a pivotal pathogenetic role. Steroid-resistant disease can be treated with immunosuppressive drugs, antimalarial therapies and recently with anti-TNFα agents. The use of biological agents for the treatment of sarcoidosis springs from research into the pathogenesis of the disease and also from the experience of rheumatologists with other chronic inflammatory diseases. Rituximab, golimumab and ustekinumab are cytokine modulators, useful in the treatment of immunoinflammatory disorders, for which randomized trials to evaluate safety and efficacy in sarcoidosis are not yet available. Novel anticytokine drugs administered alone or in association may offer a new approach to treatment of the disease. This review focuses on recent advances in anti-TNFα agents and cytokine modulators for the treatment of sarcoidosis and their therapeutic prospects.


Assuntos
Sarcoidose Pulmonar/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais Murinos/uso terapêutico , Citocinas/antagonistas & inibidores , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Pentoxifilina/uso terapêutico , Rituximab , Talidomida/uso terapêutico , Ustekinumab
14.
Pulm Med ; 2011: 717130, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21637368

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a severe, rapidly progressive diffuse lung disease. Several pathogenetic mechanisms have been hypothesized on the basis of the fibrotic lung damage occurring in this disease, and a potential profibrotic role of activated alveolar macrophages and their mediators in the pathogenesis of IPF was recently documented. This paper focuses on recent literature on potential biomarkers of IPF derived from activated alveolar macrophages. Biomarker discovery and clinical application are a recent topic of interest in the field of interstitial lung diseases (ILDs). Cytokines, CC-chemokines, and other macrophage-produced mediators are the most promising prognostic biomarkers. Many molecules have been proposed in the literature as potential biomarker of IPF; however, a rigorous validation is needed to confirm their clinical utility.

15.
Respir Med ; 105(5): 775-80, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21215607

RESUMO

A crucial pathogenetic role of serum amyloid A (SAA) in granulomatous inflammation of sarcoidosis has recently been reported. In this study we analyzed SAA expression in detail, starting from proteomic analysis of serum of sarcoidosis patients. We also used the faster ELISA method that enabled us to examine a greater number of samples. Serum concentrations of SAA were significantly higher in sarcoidosis patients than controls (p<0.001), inversely correlated with FEV(1) and significantly higher in patients with subacute onset requiring prolonged and multiple steroid treatments (class 6 SCAC) than in patients with subacute onset not requiring therapy (class 4 SCAC) (p<0.001). Our results suggest that serum amyloid A could be a suitable marker of sarcoidosis: its serum concentrations are significantly higher in sarcoidosis patients than controls, the protein is only expressed in gels of sarcoidosis patients and not in healthy subjects, and the SAA1 isoforms could match the unidentified biomarker of sarcoidosis reported in a previous proteomic study by another group. The effectiveness of SAA as a clinical biomarker of sarcoidosis should now be investigated in a large prospective study.


Assuntos
Sarcoidose Pulmonar/sangue , Proteína Amiloide A Sérica/análise , Biomarcadores/sangue , Eletroforese em Gel Bidimensional , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade
16.
Rheumatol Int ; 31(11): 1503-6, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20012958

RESUMO

Sarcoidosis is a multisystem disease of unknown origin. Granulomatous bone involvement has an overall incidence of 1-13%. This incidence is probably underestimated in certain patient series because bone involvement is often asymptomatic. The small bones of hands and feet are the most common localizations, while skull, knee, rib, pelvic and sternal localizations are rarely reported. Here we describe some interesting cases of chronic sarcoidosis with unusual bone localizations observed at our regional referral centre for sarcoidosis. We also review the literature to underline the complexity of the disease, the problem of differential diagnosis with respect to malignancies and the need for appropriate and effective therapy of this rare localization.


Assuntos
Doenças Ósseas/patologia , Doenças Raras , Sarcoidose/patologia , Alendronato/uso terapêutico , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/tratamento farmacológico , Neoplasias Ósseas/diagnóstico , Diagnóstico Diferencial , Quimioterapia Combinada , Feminino , Glucocorticoides/uso terapêutico , Humanos , Metotrexato/uso terapêutico , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Osteólise/diagnóstico por imagem , Osteólise/patologia , Radiografia , Costelas/diagnóstico por imagem , Costelas/patologia , Sarcoidose/diagnóstico por imagem , Sarcoidose/tratamento farmacológico , Crânio/diagnóstico por imagem , Crânio/patologia , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/patologia , Resultado do Tratamento
18.
Respir Med ; 103(9): 1245-56, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19464864

RESUMO

Oxidative stress is an imbalance between oxidants (reactive oxygen and nitrogen species) and antioxidants that may affect lipids, DNA, carbohydrates and proteins. The lung is continuously exposed to endogenous and exogenous oxidants (cigarette smoke, mineral dust, ozone, radiation). Reactive oxygen and nitrogen species are mainly produced by phagocytes as well as by polymorphonuclear, alveolar, bronchial and endothelial cells. A potential role of oxidative stress in the pathogenesis of diffuse lung diseases (particularly idiopathic pulmonary fibrosis) has been demonstrated. Increased oxidant levels and decreased antioxidant defences can contribute to the progression of idiopathic pulmonary fibrosis and other diffuse lung diseases. The growing number of papers on the different aspects of oxidant/antioxidant imbalance in diffuse lung diseases in the last decade reflects increasing interest in this topic and suggests that specific DLDs may be characterized by specific patterns of oxidation and antioxidant responses. The study of oxidative stress can provide insights into etiopathogenesis and favour the discovery of new treatments. In this review of the literature on oxidants and antioxidants in diffuse lung diseases, the focus is on idiopathic pulmonary fibrosis, sarcoidosis, pneumoconiosis and pulmonary fibrosis associated with systemic sclerosis.


Assuntos
Antioxidantes/metabolismo , Pneumopatias/etiologia , Oxidantes/metabolismo , Estresse Oxidativo/fisiologia , Humanos , Pulmão/metabolismo , Pneumopatias/metabolismo
19.
Respir Physiol Neurobiol ; 167(3): 261-7, 2009 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-19464392

RESUMO

By proteomic approach we previously characterised bronchoalveolar lavage (BAL) protein profiles of patients with idiopathic pulmonary fibrosis (IPF), sarcoidosis and systemic sclerosis. Among differently expressed proteins we identified macrophage migration inhibitory factor (MIF), a multi-function pleiotropic cytokine. This study was performed to validate our findings by a further proteomic approach and ELISA in a larger population of patients and controls. MIF expression in lung tissue was also evaluated by immunohistochemistry. MIF was identified in all 2-DE gels of IPF patients and it was significantly increased compared to controls (p<0.05). This result was confirmed by ELISA: MIF concentrations were significantly higher in IPF patients than controls (p<0.001) and were directly correlated with neutrophil percentages (p=0.0095). Immunohistochemical analysis revealed enhanced expression in bronchiolar epithelium, alveolar epithelium, and fibroblastic foci. In conclusion, MIF is a pleiotropic cytokine that could be involved in the pathogenesis of IPF, being particularly abundant in BAL of these patients and mainly expressed in the areas of active fibrosis.


Assuntos
Fatores Inibidores da Migração de Macrófagos/sangue , Fibrose Pulmonar/sangue , Adulto , Idoso , Gasometria , Líquido da Lavagem Broncoalveolar/citologia , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Testes de Função Respiratória , Fumar/efeitos adversos
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